(R01) Strengthening the Evidence-Base to Support Medication Prescribing in Older Adults with Chronic Kidney Disease

Rutgers Biomedical And Health Sciences, Newark NJ

Investigators

Abstract

Chronic kidney disease (CKD) affects 40% of older adults (≥65 years), and is a significant contributor to morbidity, mortality, and healthcare spending. Although older adults with CKD are more likely to be diagnosed with multiple chronic conditions, take multi-drug regimens, and owing to pharmaco- dynamic and -kinetic modulations, are uniquely susceptible to experiencing drug-related harms, they are routinely excluded from clinical trials. Thus, there is an urgent need to examine the safety and effectiveness of medications in this population. In response to this unmet need, this proposal will study the effects of medications in older CKD adults. We will focus on cardiometabolic drugs as such factors are the most frequent complications of CKD (e.g. cardiovascular diseases [CVD]). Specific medications were selected for study based on the criteria of high and rising prevalence of use, potential for fatal harms, concerns for ineffectiveness, and unmet clinical need. We will primarily use the national Veterans Affairs data, and externally validate findings in a large EHR database. Aim 1 will evaluate the role of renoprotective therapies (e.g. angiotensin converting enzyme inhibitors; ACEi) in sustaining long-term kidney function among patients initiating: ACEi vs other antihypertensives (Aim 1a), and sodium-glucose co-transporter-2 inhibitors vs other glucose-lowering therapies (Aim 1b). Aim 2 will elucidate the benefit-risk profiles of newer CVD medications by comparing the incidence of CVD endpoints and major bleeding in patients initiating: direct acting oral anticoagulants vs warfarin (Aim 2a), and newer antiplatelet drugs (e.g. ticagrelor) vs clopidogrel (Aim 2b). Our central hypotheses are that (a) due to a confluence of factors (e.g. low prevalence of proteinuria), renoprotective medications have limited effectiveness in sustaining kidney function; and (b) kidney disease and older age alter the benefit-risk profiles of medications. The expected impact of this proposal is significant as it will generate the requisite evidence base to support drug prescribing in this critically understudied population, impacting 40% of older adults who have CKD. Given the paucity of data from clinical trials, these findings will serve as the primary source of drug information for patients, caregivers, and clinicians to make informed decisions. We believe that this proposal outlines the most effective, valid, and feasible way to generate clinically relevant evidence pertaining to medication effects in older adults with CKD.